Abstract
Pyrimidino-thiazolyl carbonitriles were prepared that are potent VEGFR-2 (KDR) kinase inhibitors. The modification of lead structures resulted in 3m which exhibited the best overall profile in KDR inhibitory activity, iv/po pharmacokinetics, and reduced hERG affinity.
MeSH terms
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Animals
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Dogs
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Macaca mulatta
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Molecular Structure
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Nitriles / chemical synthesis*
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Nitriles / chemistry
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Nitriles / pharmacology*
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Rats
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Sensitivity and Specificity
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / chemistry
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Thiazoles / pharmacology*
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
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Nitriles
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Protein Kinase Inhibitors
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Pyrimidines
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Thiazoles
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Vascular Endothelial Growth Factor Receptor-2